Abstract
Spasticity is an important problem that complicates daily living in many individuals with spinal cord injury (SCI). While previous studies in human and animals revealed significant improvements in locomotor ability with treadmill locomotor training, it is not known to what extent locomotor training influences spasticity. In addition, it would be of considerable practical interest to know how the more ergonomically feasible cycle training compares with treadmill training as therapy to manage SCI-induced spasticity and to improve locomotor function. Thus the main objective of our present studies was to evaluate the influence of different types of locomotor training on measures of limb spasticity, gait, and reflex components that contribute to locomotion. For these studies, 30 animals received midthoracic SCI using the standard Multicenter Animal Spinal cord Injury Studies (MASCIS) protocol (10 g 2.5 cm weight drop). They were divided randomly into three equal groups: control (contused untrained), contused treadmill trained, and contused cycle trained. Treadmill and cycle training were started on post-injury day 8. Velocity-dependent ankle torque was tested across a wide range of velocities (612–49°/s) to permit quantitation of tonic (low velocity) and dynamic (high velocity) contributions to lower limb spasticity. By post-injury weeks 4 and 6, the untrained group revealed significant velocity-dependent ankle extensor spasticity, compared to pre-surgical control values. At these post-injury time points, spasticity was not observed in either of the two training groups. Instead, a significantly milder form of velocity-dependent spasticity was detected at postcontusion weeks 8–12 in both treadmill and bicycle training groups at the four fastest ankle rotation velocities (350–612°/s). Locomotor training using treadmill or bicycle also produced significant increase in the rate of recovery of limb placement measures (limb axis, base of support, and open field locomotor ability) and reflex rate-depression, a quantitative assessment of neurophysiological processes that regulate segmental reflex excitability, compared with those of untrained injured controls. Light microscopic qualitative studies of spared tissue revealed better preservation of myelin, axons, and collagen morphology in both locomotor trained animals. Both locomotor trained groups revealed decreased lesion volume (rostro-caudal extension) and more spared tissue at the lesion site. These improvements were accompanied by marked upregulation of BDNF, GABA/GABAb, and monoamines (e.g., norepinephrine and serotonin) which might account for these improved functions. These data are the first to indicate that the therapeutic efficacy of ergonomically practical cycle training is equal to that of the more labor-intensive treadmill training in reducing spasticity and improving locomotion following SCI in an animal model.
Highlights
Spinal cord injury (SCI) produces a number of complicated challenges to the recovery of locomotor function, retraining the residual nervous system to overcome obstacles posed by the loss of connectivity diminished by injury or enhanced by non-adaptive plasticity
Such locomotor training uses principles derived from animal and human studies showing that stepping can be generated by virtue of the neuromuscular system’s responsiveness to phasic, peripheral sensory information associated with locomotion (Lovely et al, 1986, 1990; Barbeau and Rossignol, 1987; Edgerton et al, 1997, 2004; Harkema et al, 1997; de Leon et al, 1998; Behrman and Harkema, 2000)
VELOCITY-DEPENDENT ANKLE TORQUE AND ASSOCIATED EMGS Baseline measures of velocity-dependent ankle torques and extensor EMGs were obtained from all animals before injury (Figures 2A,B), at post-injury weeks 1 and 2, and at alternate weeks up to po week 12
Summary
Spinal cord injury (SCI) produces a number of complicated challenges to the recovery of locomotor function, retraining the residual nervous system to overcome obstacles posed by the loss of connectivity diminished by injury or enhanced by non-adaptive plasticity. Recent evidence indicates that individuals with complete and incomplete SCIs improve their ability to step on a treadmill, to cycle or walk overground following specific locomotor training (Visintin and Barbeau, 1989; Wernig and Muller, 1992; Dietz et al, 1994; Wernig et al, 1995; Harkema et al, 1997; Behrman and Harkema, 2000; and see reviews, Barbeau et al, 1999; Basso, 2000; Wolpaw and Tennissen, 2001; Dietz and Harkema, 2004) Such locomotor training uses principles derived from animal and human studies showing that stepping can be generated by virtue of the neuromuscular system’s responsiveness to phasic, peripheral sensory information associated with locomotion (Lovely et al, 1986, 1990; Barbeau and Rossignol, 1987; Edgerton et al, 1997, 2004; Harkema et al, 1997; de Leon et al, 1998; Behrman and Harkema, 2000). The purpose of the present studies was to utilize these biomechanical, behavioral, and neurophysiological measures in this model of SCI to (1) provide preclinical data on quantitative assessment of the influence of locomotor training on lower limb spasticity, (2) to correlate these changes with neurophysiological processes that regulate reflex excitability, and (3) to compare potential benefits of treadmill vs. bicycle locomotor training
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